Dehydrogenation and oxidation metabolism of harmaline into harmine

[Woolmer]

I'm struggling to fully understand this paper, but thought it is quite interesting.

Abstract
Harmaline can be transformed into harmine after oral administration. However, enzymes involved in the metabolic pathway remain unclear. In this study, harmaline was incubated with rat liver microsomes (RLM), rat brain microsomes (RBM), blood, plasma, broken blood cells, and heme peroxidases including horseradish peroxidase (HRP), lactoperoxidase (LPO), and myeloperoxidase (MPO). The production of harmine was determined by a validated UPLC-ESI-MS/MS method. Results showed that heme peroxidases catalyzed the oxidative dehydrogenation of harmaline. All the reactions were in accordance with the Hill equation. The reaction was inhibited by ascorbic acid and excess H2O2. The transformation of harmaline to harmine was confirmed after incubation with blood, plasma, and broken blood cells, rather than RLM and RBM. Harmaline was incubated with blood, plasma, and broken cells liquid for 3 h, and the formation of harmine became stable. Results indicated an integrated metabolic pathway of harmaline, which will lay foundation for the oxidation reaction of dihydro-β-carboline. Moreover, the metabolic stability of harmaline in blood should not be ignored when the pharmacokinetics study of harmaline is carried out.

Heme peroxidases are responsible for the dehydrogenation and oxidation metabolism of harmaline into harmine

 

[ShadedSelf]

Really interesting.

Sounds like they were researching the mechanisms that turn harmaline into harmine in the body, which seems to happen from the presence of peroxidases in the blood.

Also, hopefully someone with chemistry knowledge can clarify, but it looks like with something like horseradish peroxidase and H2O2 one could turn harmaline into harmine.
Not sure how easy it is to get a hold of this enzymes though.

 

[downwardsfromzero]

It's not entirely clear from the paper whether the blood fluids used were of rat or human origin. Rat metabolism can't be entirely reliably extrapolated onto human metabolism so it remains to be seen if the conversion of harmaline to harmine occurs in vivo in human blood. There might be some metabolic studies on the fate of harmala alkaloids in ayahuasca users (I've not looked) but then it's worth noting that typical ayahuasca sample contain a preponderance of harmine and THH while, in contrast, having little in the way of harmaline content.

As far as enzymes go, one could in principle extract horseradish peroxidase from horseradish roots if purchasing from a biochemical supply house turned out to be too tricky.

Many materials have been explored to mimic natural HRP. For example, iron oxide nanoparticles and hemin-containing complexes have been used to mimic HRP.[12] These HRP-like artificial enzymes have been used for many applications, ranging from biomarker detection and tumor immunostaining to antibiofouling.

It might be a little much to go to the trouble of designing a custom enzyme mimic for this reaction but who knows?